Systematic Phenomics Analysis Deconvolutes Genes Mutated in Intellectual Disability into Biologically Coherent Modules

Kochinke K, Zweier C, Nijhof B, Fenckova M, Cizek P, Honti F, Keerthikumar S, Oortveld MAW, Kleefstra T, Kramer JM, Webber C, Huynen MA, Schenck A (2016)

Publication Type: Journal article

Publication year: 2016

Journal

American Journal of Human Genetics Elsevier (Cell Press)

Book Volume: 98

Pages Range: 149-64

Journal Issue: 1

DOI: 10.1016/j.ajhg.2015.11.024

Abstract

Intellectual disability (ID) disorders are genetically and phenotypically extremely heterogeneous. Can this complexity be depicted in a comprehensive way as a means of facilitating the understanding of ID disorders and their underlying biology? We provide a curated database of 746 currently known genes, mutations in which cause ID (ID-associated genes [ID-AGs]), classified according to ID manifestation and associated clinical features. Using this integrated resource, we show that ID-AGs are substantially enriched with co-expression, protein-protein interactions, and specific biological functions. Systematic identification of highly enriched functional themes and phenotypes revealed typical phenotype combinations characterizing process-defined groups of ID disorders, such as chromatin-related disorders and deficiencies in DNA repair. Strikingly, phenotype classification efficiently breaks down ID-AGs into subsets with significantly elevated biological coherence and predictive power. Custom-made functional Drosophila datasets revealed further characteristic phenotypes among ID-AGs and specific clinical classes. Our study and resource provide systematic insights into the molecular and clinical landscape of ID disorders, represent a significant step toward overcoming current limitations in ID research, and prove the utility of systematic human and cross-species phenomics analyses in highly heterogeneous genetic disorders.

Authors with CRIS profile

Christiane Zweier Lehrstuhl für Humangenetik

Involved external institutions

Radboud University Nijmegen NL Netherlands (NL) University of Oxford GB United Kingdom (GB)

How to cite

APA:

Kochinke, K., Zweier, C., Nijhof, B., Fenckova, M., Cizek, P., Honti, F.,... Schenck, A. (2016). Systematic Phenomics Analysis Deconvolutes Genes Mutated in Intellectual Disability into Biologically Coherent Modules. American Journal of Human Genetics, 98(1), 149-64. https://doi.org/10.1016/j.ajhg.2015.11.024

MLA:

Kochinke, Korinna, et al. "Systematic Phenomics Analysis Deconvolutes Genes Mutated in Intellectual Disability into Biologically Coherent Modules." American Journal of Human Genetics 98.1 (2016): 149-64.

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